PART I. While a role for elevated plasma AVP levles has been confirmed in a variety of hypoosmolar syndromes, little information exists regarding alterations in AVP receptor function in these states. Utliizing an in vitro renal medullary membrane preparation, the present study proposes to compare radiolabelled AVP binding to its receptor in normal controls and in experimental models of chronic AVP excess. The results will be subjected to Scatchard analysis to determine AVP receptor concentration and binding affinity. The biological significance of alterations in AVP receptor properties will be determined by evaluating adenylate cyclase responsiveness to AVP stimulation in control and experimental animals. The results should help elucidate the biochemcial basis for the role of AVP in hypoosmolar states. PART II. Recently d(CH2)5Tyr(Et)VAVP, an antagonist to the hydroosmotic effects of AVP has been synthesized. Using the in vitro techniques outlined in Part I, the relative binding affinity of this AVP analogue will be determined; the mechanism of its inhibitory action (competitive or noncompetitive) will be assessed; and any partial agonist activity will be determined. These results should have important therapeutic implications for the treatment of hypoosmolar states.